Copes Francesco, Pien Nele, Van Vlierberghe Sandra, Boccafoschi Francesca, Mantovani Diego
Laboratory for Biomaterials and Bioengineering, Canada Research Chair Tier I for the Innovation in Surgery, Department of Min-Met-Materials Engineering & Regenerative Medicine, CHU de Quebec Research Center, Laval University, Quebec City, QC, Canada.
Laboratory of Human Anatomy, Department of Health Sciences, University of Piemonte Orientale, Novara, Italy.
Front Bioeng Biotechnol. 2019 Jul 12;7:166. doi: 10.3389/fbioe.2019.00166. eCollection 2019.
Cardiovascular diseases (CVDs) account for the 31% of total death per year, making them the first cause of death in the world. Atherosclerosis is at the root of the most life-threatening CVDs. Vascular bypass/replacement surgery is the primary therapy for patients with atherosclerosis. The use of polymeric grafts for this application is still burdened by high-rate failure, mostly caused by thrombosis and neointima hyperplasia at the implantation site. As a solution for these problems, the fast re-establishment of a functional endothelial cell (EC) layer has been proposed, representing a strategy of crucial importance to reduce these adverse outcomes. Implant modifications using molecules and growth factors with the aim of speeding up the re-endothelialization process has been proposed over the last years. Collagen, by virtue of several favorable properties, has been widely studied for its application in vascular graft enrichment, mainly as a coating for vascular graft luminal surface and as a drug delivery system for the release of pro-endothelialization factors. Collagen coatings provide receptor-ligand binding sites for ECs on the graft surface and, at the same time, act as biological sealants, effectively reducing graft porosity. The development of collagen-based drug delivery systems, in which small-molecule and protein-based drugs are immobilized within a collagen scaffold in order to control their release for biomedical applications, has been widely explored. These systems help in protecting the biological activity of the loaded molecules while slowing their diffusion from collagen scaffolds, providing optimal effects on the targeted vascular cells. Moreover, collagen-based vascular tissue engineering substitutes, despite not showing yet optimal mechanical properties for their use in the therapy, have shown a high potential as physiologically relevant models for the study of cardiovascular therapeutic drugs and diseases. In this review, the current state of the art about the use of collagen-based strategies, mainly as a coating material for the functionalization of vascular graft luminal surface, as a drug delivery system for the release of pro-endothelialization factors, and as physiologically relevant vascular models, and the future trend in this field of research will be presented and discussed.
心血管疾病（CVDs）占每年总死亡人数的31%，是全球首要死因。动脉粥样硬化是最危及生命的心血管疾病的根源。血管搭桥/置换手术是动脉粥样硬化患者的主要治疗方法。用于此应用的聚合物移植物仍因高失败率而负担沉重，主要是由植入部位的血栓形成和新生内膜增生引起的。作为解决这些问题的方法，有人提出快速重建功能性内皮细胞（EC）层，这是减少这些不良后果的关键策略。在过去几年中，人们提出了使用分子和生长因子对植入物进行修饰，以加速再内皮化过程。胶原蛋白由于具有多种有利特性，已被广泛研究用于血管移植物强化，主要作为血管移植物管腔表面的涂层以及作为释放促内皮化因子的药物递送系统。胶原蛋白涂层在移植物表面为内皮细胞提供受体-配体结合位点，同时作为生物密封剂，有效降低移植物孔隙率。基于胶原蛋白的药物递送系统的开发已得到广泛探索，在该系统中，小分子和蛋白质类药物被固定在胶原蛋白支架内，以控制其在生物医学应用中的释放。这些系统有助于保护负载分子的生物活性，同时减缓其从胶原蛋白支架中的扩散，对靶向血管细胞产生最佳效果。此外，基于胶原蛋白的血管组织工程替代物尽管尚未显示出用于治疗的最佳机械性能，但已显示出作为研究心血管治疗药物和疾病的生理相关模型的巨大潜力。在本综述中，将介绍和讨论基于胶原蛋白策略的当前技术水平，主要作为血管移植物管腔表面功能化的涂层材料、作为释放促内皮化因子的药物递送系统以及作为生理相关血管模型，以及该研究领域的未来趋势。
